Osteoporosis leads to substantial disability and mortality in postmenopausal women. Corticosteroids currently represent the most effective anti-inflammatory treatment of asthma. Because they are thought to produce fewer of the deleterious systemic effects of orally administered corticosteroids, use of inhaled corticosteroids has been advocated by task forces on the treatment of asthma. Corticosteroids produce negative calcium balance, inhibit bone formation, and increase bone resorption. Despite a longstanding association between osteoporotic fractures and oral corticosteroid use, particularly in postmenopausal women, knowledge of the effects of inhaled corticosteroids on bone loss have not been determined. Several lines of evidence suggest that inhaled corticosteroids adversely affect bone homeostasis, these include data showing a rapid suppression of osteocalcin levels, a marker of bone formation, and data from one cross-sectional study which showed a decrease in total body calcium in patients treated with inhaled corticosteroids, including a subset who had not been previously treated with prior oral corticosteroids. Recent data suggest that estrogen-progesterone therapy may prevent bone loss in corticosteroid-treated women, possibly by antagonizing some of the skeletal effects of corticosteroids on calcium balance and bone turnover. The development of bone density techniques such as dual X-ray absorptiometry makes it feasible to reproducibly and accurately detect small prospective changes in bone density. Moreover, the availability of serum osteocalcin and urinary collagen crosslink levels provides sensitive and specific markers of bone formation and resorption, respectively. Thus the overall goal of this proposal is to define whether inhaled corticosteroids produce a dose-dependent effect on bone density and indices of skeletal turnover in postmenopausal women and whether estrogen-progesterone therapy attenuates these adverse effects on bone. The resulting information will represent a major step in determining the safety of inhaled corticosteroids in postmenopausal women at risk for osteoporotic fractures.